The recently isolated and characterized bone morphogenetic proteins (BMPs) induce endochondral bone differentiation in vivo. Molecular cloning and expression of human recombinant BMPs may provide the potential for controlled initiation of bone regeneration and repair in man. While substantial progress is being made in the elucidation of the molecular and cellular mechanisms involved in BMP- induced bone differentiation, the morphogenetic potential of BMPs is predominantly based on work in rodents.The long-term objective of the proposed research is to study the efficacy and safety of native and recombinant BMPs delivered by suitable carriers in a nonhuman primate model. This work has relevance to the repair and regeneration of bone in congenital and acquired craniofacial anomalies in man. The applicant proposes to investigate the efficacy and safety of native and recombinant BMPs using nonhealing calvarial defects of adult male baboons (Papio ursinus). The specific aims are first, to determine the optimal dose of recombinant human BMP that will elicit a repair comparable to native BMPs; Second, to determine if the rate and extent of bone formation can be accelerated by increasing doses of recombinant BMP; third, to determine the fate and long term remodeling of the newly induced bone by recombinant BMP. Histology and histomorphometry will be used to quantitate the extent of bone regeneration induced by different doses of human recombinant BMP (HrBMP) at different observation periods, and delivered either by collagenous matrix or porous hydroxyapatite substrata.